Abstract
Increasing evidence suggests that the pathogenesis of chronic obstructive pulmonary disease (COPD) is associated with FUN14 domain protein 1 (FUNDC1)-mediated mitophagy. Recently, studies have reported that puerarin has protective effects against excessive oxidative damage in cells. Therefore, we hypothesized that puerarin may be involved in COPD progression via regulating FUNDC1 mediated mitophagy. We found that the viability of cigarette smoke extract (CSE)-stimulated human bronchial epithelial cells (HBECs) was enhanced and apoptosis was reduced after treatment with different concentrations of puerarin. Puerarin reversed mitochondrial membrane potential (MMP) levels and ATP content, and decreased reactive oxygen species (ROS) content in CSE stimulated HBECs. Moreover, puerarin significantly inhibited apoptosis related proteins, as well as the expression of mitophagy related proteins. After inhibition of FUNDC1 phosphorylation by protein phosphatase inhibitor (PH0321), puerarin restored MMP level, decreased ROS content, promoted ATP synthesis, and downregulated autophagy related protein expression in HBECs. In addition, mitochondrial division inhibitor (Mdivi) inhibited the expression of autophagy related proteins and reduced apoptosis after blocking cell autophagy, which was the same as the inhibition of puerarin. Finally, puerarin activated the PI3K/Akt/mTOR signaling pathway to participate in COPD progression by up regulating the phosphorylation levels of PI3K, Akt and mTOR.
Highlights
Chronic obstructive pulmonary disease (COPD) is a common disease characterized by persistent airflow limitation, and its clinical manifestations are mainly chronic cough, shortness of breath, chest tightness or wheezing [1, 2]
The results of flow cytometry showed that the apoptosis of human bronchial epithelial cells (HBECs) treated with 20% cigarette smoke extract (CSE) was significantly increased, but this trend was reversed after puerarin intervention at different concentrations, and the inhibition of apoptosis by high concentrations of puerarin was more significant (Figure 1B)
The changes of membrane potential (MMP) level were detected by flow cytometry after labeling with JC-1 probe and the results showed that MMP level was significantly decreased after 20% CSE treatment, suggesting early apoptosis of cells
Summary
Chronic obstructive pulmonary disease (COPD) is a common disease characterized by persistent airflow limitation, and its clinical manifestations are mainly chronic cough, shortness of breath, chest tightness or wheezing [1, 2]. Persistent chronic inflammation induces the recurrence of tracheal wall injury and repair process, leading to airway remodeling, which is the main cause of irreversible progression of COPD [3, 4]. It has been shown that cigarette smoke extract (CSE)-stimulated human bronchial epithelial cells (HBECs) exhibit stronger mitophagy [7, 8]. In COPD progression, mammalian mitotic receptor FUN14 domain protein 1 (FUNDC1) is closely related to autophagy and apoptosis in hypoxic cells, which can participate in mitosis through enhanced mitophagy [9]. Wen et al found that silencing the FUNDC1 gene in CSE-stimulated HBECs, the expression of DRP1 was inhibited, inhibiting mitophagy and apoptosis and slowing down the COPD process [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
